The National Marrow Donor Program (NMDP) was established in 1987 to: 1.) create a registry of volunteer, tissue-typed, unrelated bone marrow donors; and 2.) facilitate matched unrelated donor marrow transplants through a coordinated circuit of Donor Centers, Collection Centers, and Transplant Centers. As of July 1998, 3.2 million donors were participating in the registry and 6,700 unrelated marrow transplants had been performed. In transplant recipients with early graft loss, the best option for therapy is often another dose of stem cells from the original marrow donor. Peripheral blood stem cell (PBSC) components, harvested by apheresis of filgrastim-stimulated donors, provide larger numbers of hematopoietic progenitor cells that engraft more rapidly than marrow-derived cells. For these reasons, a protocol involving all participating NMDP Donor Centers was initiated in February 1997, for the acquisition of PBSCs for second transplants. The objectives of the study are: 1.) to monitor the immediate and long-term safety of filgrastim administration in healthy volunteer donors; 2.) to compare the adverse effects of bone marrow versus PBSC donation; and 3.) to monitor the outcome of matched unrelated-donor PBSC transplants, including time to engraftment, incidence of acute and chronic GVHD, and disease-free and overall survival rates. As of August 1998, 33 unrelated NMDP donors received filgrastim 10 ug/kg/day SQ for 5 days, followed by apheresis. Seventeen donors underwent one procedure, 15 underwent two, and none required central line placement. All donors experienced granulocyte colony stimulating factor-induced fatigue, insomnia, bone pain or headache, although in only 6 percent of donors were these effects considered severe. Peak mean leukocyte counts after filgrastim were 46 ' 12 x 10 to the 9th power/L, and postapheresis thrombocytopenia (less than 100 x 10 to the 9th power/L) occurred 5 donors (15 percent), all of whom underwent two procedures. The mean time to complete recovery from PBSC donation was 1 week, compared with 3 weeks for marrow harvest. Product CD34 content, and recipient outcomes, including time to engraftment, acute and chronic GVHD in the recipient, and overall survival have not yet been evaluated.The NIH Marrow Donor Center, a participant in the NMDP, has 48,000 donors on its registry. One hundred eighty-five NIH unrelated donors have undergone marrow harvest and six have undergone PBSC donation for NMDP recipients. Sufficient cells for transplant were obtained in one 12'18 liter apheresis procedure in all six cases. The availability of same-day CD34 flow analysis permitted exact quantitation of product content and avoided the need for additional apheresis procedures. Five of six donors preferred PBSC donation by apheresis to marrow harvest due to the lack of need for anesthesia and hospitalization. The discomfort of the two procedures was considered equivalent.Two of the principal investigators for this national study are in the DTM/CC (SFL and DS). Administrative and statistical support for the study are provided by the NMDP National Office. Filgrastim is provided under an Investigational New Drug agreement with Amgen (BB-IND # 6821).